Hongfang Yang; Patricia F. Medeiros; Kaushik Raha; Patricia Elkins; Kenneth E. Lind; Ruth Lehr; Nicholas D. Adams; Joelle L. Burgess; Stanley J. Schmidt; Steven D. Knight; Kurt R. Auger; Michael D. Schaber; G. Joseph Franklin; Yun Ding; Jennifer L. DeLorey; Paolo A. Centrella; Sibongile Mataruse; Steven R. Skinner; Matthew A. Clark; John W. Cuozzo; Ghotas Evindar
ACS Med. Chem. Lett., 2015, 6, 5, 531-536
https://doi.org/10.1021/acsmedchemlett.5b00025

Abstract

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.